Abstract
Development of nonviral gene transfer methods would be a valuable addition to the gene-therapy armamentarium, particularly for localized targeting of specific tissue volumes. Ultrasound can produce a variety of nonthermal bioeffects via acoustic cavitation including DNA delivery. Cavitation bubbles may induce cell death or transient membrane permeabilization (sonoporation) on a single cell level, as well as microvascular hemorrhage and disruption of tissue structure. Application of sonoporation for gene delivery to cells requires control of cavitation activity. Many studies have been performed using in vitro exposure systems, for which cavitation is virtually ubiquitous. In vivo, cavitation initiation and control is more difficult, but can be enhanced by cavitation nucleation agents, such as an ultrasound contrast agent. Sonoporation and ultrasonically enhanced gene delivery has been reported for a wide range of conditions including low frequency sonication (kilohertz frequencies), lithotripter shockwaves, HIFU, and evendiagnostic ultrasound (megahertz frequencies). In vitro, a variety of cell lines has been successfully transfected, with concomitant cell killing. In vivo, initial applications have been to cancer gene therapy, for which cell killing can be a useful simultaneous treatment, and to cardiovascular disease. The use of ultrasound for nonviral gene delivery has been demonstrated for a robust array of in vitro and mammalian systems, which provides a fundamental basis and strong promise for development of new gene therapy methods for clinical medicine.
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Literature Cited
Nabel EG. Circulation 1995; 91:541–548.
Schneider MD, French B. Circulation 1993; 88:1937–1942.
Gershon H, Ghirlando R, Gutman SB et al. Biochemistry 1993; 32:7143–7151.
Chang DC, Reese TS. Biophys J 1990; 58:1–12.
Daniell H. Methods Enzymol 1993; 217:536–557.
Newman CM, Lawrie A, Brisken AF et al. Echocardiography 2001; 18:339–347.
Kim HJ, Greenleaf JF, Kinnick RR et al. Hum Gene Ther 1996; 7:1339–1346.
Bao S, Thrall BD, Miller DL. Ultrasound Med Biol 1997; 23:953–959.
Tata DB, Dunn F, Tindall DJ. Biochem Biophys Res Comm 1997; 234:64–67.
Greenleaf, WJ, Bolander ME, Sarkar G et al. Ultrasound Med Biol 1998; 24:587–595.
Mukherjee D, Wong J, Griffin B et al. J Am Coll Cardiol 2000; 35:1678–1686.
Porter TR, Iversen PL, Li S et al. J Ultrasound Med 1996; 15:577–584.
Lawrie A, Briskin AF, Francis SE et al. Gene Ther 2000; 7:2023–2027.
Shohet RV, Chen S, Zhou Y et al. Circulation 2000; 101:2554–2556.
Yamasaki K, Tachibana T, Taniyama Y. Circulation 2000; 102:II-247.
Komamura K, Tatsumi R, Miyatake K. Circulation 2000; 102:II-561.
Taniyama Y, Tachibana K, Yamamoto K. Circulation 2000; 102:II-164.
Amabile PG, Waugh JM, Lewis TN et al. Circulation 2000; 102:II-147.
Fu YK, Kaufman GE, Miller MW et al. Radiat Res 1979; 80:575–580.
Mortimer AJ, Dyson M. Ultrasound Med Biol 1988; 14:499–506.
Dinno MA, Crum LA, Wu J. Ultrasound Med Biol 1989; 15:461–470.
Mihran RT, Barnes FS, Wachtel H. Ultrasound Med Biol 1990; 16:297–309.
Pohl EE, Rosenfeld EH, Pohl P et al. Ultrasound Med Biol 1995; 21:711–719.
Kaufman GE, Miller MW. Ultrasound Med Biol 1978 4:139–144.
Miller DL, Thomas RM, Buschbom RL. Ultrasound Med Biol 1995; 21:841–848.
Liebeskind D, Bases R, Mendez F et al. Science 1979; 205:1273–1275.
Miller MW, Miller DL, Brayman AA. Ultrasound Med Biol 1996; 22:1131–1154.
Kaufman GE. Ultrasound Med Biol 1985; 11:497–501.
Dalecki D, Keller BB, Raeman CH et al. Ultrasound Med Biol 1993; 19:385–390.
MacRobbie AG, Raeman CH, Child SZ et al. Ultrasound Med Biol 1997; 23:761–765.
Skyba DM, Price RJ, Linka AZ et al. Circulation 1998; 98:290–293.
Miller DL, Quddus J. Proc Natl Acad Sci USA 2000; 97:10179–10184.
Hynynen K, Chung AH, Colucci V et al. Ultrasound Med Biol 1996; 22:193–201.
Child SZ, Hartman CL, Schery LA et al. Ultrasound Med Biol 1990; 16:817–825.
Tarantal AF, Canfield DR. Ultrasound Med Biol 1994; 20:65–72.
Zachary JF, O'Brien WD, Jr. Vet Pathol 1995; 32:43–54.
Miller DL, Thomas RM. Ultrasound Med Biol 1995; 21:249–257.
Dalecki D, Child SZ, Raeman CH et al. J Acoust Soc Am 1995; 97:3165–3170.
Ramnarine KV, Nassiri DK, McCarthy A et al. Ultrasound Med Biol 1998; 24:575–585.
Tsirulnikov EM, Vartanyan IA, Gersuni GV et al. Ultrasound Med Biol 1998; 14:277–285.
Nilsson AM, Odselius R, Roijer A et al. Ultrasound Med Biol 1995; 21:833–840.
Tachibana K, Tachibana S. Circulation 1995; 92:1148.
Harrison GH, Balcer-Kubiczek EK, Eddy HA. Int J Rad Biol 1991; 59:1453–1466.
Saad AH, Hahn GM. Ultrasound Med Biol 1992; 18:715–723.
Price RJ, Skyba DM, Kaul S et al. Circulation 1998; 98:1264–1267.
Unger EC, McCreery TP, Sweitzer RH et al. Invest Radiol 1998; 33:886–892.
Ter Haar G. Ultrasound Med Biol 1995; 21:1089–1100.
Bender LF, Janes JM, Herrick JF. Arch Phys Med Rehabil 1954; 35:555.
Duarte LR. Arch Orthop Trauma Surg 1983; 101:153–159.
Nyborg WL, Carson PL, Miller MW et al. Biological Effects of Ultrasound: Mechanisms and Clinical Implications, Report No. 74, National Council on Radiation Protection and Measurements, Bethesda, MD, 1983.
Nyborg WL, Carson PL, Miller MW et al. Exposure Criteria for Medical Diagnostic Ultrasound: I. Criteria Based on Thermal Mechanisms, National Council on Radiation Protection Report No 113, Bethesda, MD, 1992.
American Institute of Ultrasound in Medicine. J Ultrasound Med 2000; 19:69–168.
Ter Haar G, Duck FA. (eds.). The Safe Use of Ultrasound in Medical Diagnosis, British Medical Ultrasound Society/The British Institute of Radiology, London, 2000.
Whittingham TA. in Ultrasound in Medicine, FA Duck, AC Baker, HC Staritt (eds.), Institute of Physics Publishing, Philadelphia, 1998.
Dalecki D, Child SZ, Raeman CH et al. Ultrasound Med Biol 1997; 23:777–781.
Roy RA, Atchley AA, Crum LA et al. J Acoust Soc Am 1985; 78:1799–1805.
Clarke PR, Hill CR. J Acoust Soc Am 1970; 47:649–653.
Fechheimer M, Denny D, Murphy RF et al. Eur J Cell Biol 1986; 40:242–247.
Fechheimer M, Boylan JF, Parker S et al. Proc Natl Acad Sci USA 1987; 84:8463–8467.
Johannes C, Obe G. Mutat Res 1997; 374:245–251.
Delius M. Shock Waves 1994; 4:55–72.
Gambihler S, Delius M, Ellwart JW. J Memb Biol 1994; 141:267–275.
Delius M, Adams G. Cancer Res 1999; 59:5227–5232.
Miller DL, Williams AR, Morris JE et al. Ultrasonics 1998; 36:947–952.
Zhong P, Haifan L, Xi X et al. J Acoust Soc Am 1999; 105:1997–2009.
Doukas AG, Flotte TJ. Ultrasound Med Biol 1996; 22:151–164.
Lee S, McAuliffe DJ, Zhang H et al. Ultrasound Med Biol 1997; 23:1089–1094.
Mulholland SE, Lee S, McAuliffe DJ et al. Pharm Res 1999; 16:514–518.
Miller DL, Bao S, Morris JE. Ultrasound Med Biol 1999; 25:143–149.
Ward M, Wu J, Chiu J. J Acoust Soc Am 1999; 105:2951–2957.
Ward M, Wu J, Chiu J. Ultrasound Med Biol 2000; 26:1169–1175.
Miller DL, Quddus J. Ultrasound Med Biol 2000; 26:661–667.
Joersbo M, Brunstedt J. Plant Cell Rep 1990; 9:207–210.
Joersbo M, Brunstedt J. Physiol Plantar 1992; 85:230–234.
Joersbo M, Brunstedt J. J Virol Methods 1990; 29:63–69.
Zhang L, Cheng L, Xu N, Zhao N et al. Biotechnology 1991; 9:996–997.
Wyber JA, Andrews J, D'Emanuele A. Pharma Res 1997; 14:750–756.
Lauer U, Burgelt E, Squire Z et al. Gene Ther 1997; 4:710–715.
Miller DL, Bao S, Gies RA et al. Ultrasound Med Biol 1999; 25:1425–1430.
Huber PE, Jenne J, Debus J et al. Ultrasound Med Biol 1999; 25:1451–1457.
Huber PE, Pfisterer P. Gene Ther 2000; 7:1516–1525.
Lawrie A, Briskin AF, Francis SE et al. Circulation 1999; 99:2617–2620.
Manome Y, Nakamura M, Ohno T et al. Hum Gene Ther 2000; 11:1521–1528.
Koch S, Pohl P, Cobet U et al. Ultrasound Med Biol 2000; 26:897–903.
Delius M, Hofschneider P, Lauer U et al. Lancet 1995; 345:1377.
Bao S, Thrall BD, Gies RA et al. Cancer Res 1998; 58:219–221.
Anwer K, Kao G, Proctor B, Anscombe I et al. Gene Ther 2000; 7:1833–1839.
Tomizawa M, Ebara M, Saisho H et al. Cancer Lett 2001; 173:31–38.
Porter TR, Kricsfeld D, Xie F. J Am Soc Echocardiogr 2000; 13:434.
Cooper MJ. Semin Oncol 1996; 23:172–187.
Berinstein NL. Biological therapy of cancer, In The Basic Science of Oncology, 3rd edn., IF Tannock, RP Hill (eds.), McGraw Hill, New York, Chap. 18, 1998.
Nomura T, Nakajima S, Kawabata K et al. Cancer Res 1997; 57:2681–2686.
Yang JP, Huang L. Gene Ther 1996; 3:542–548.
Rakhmilevich AL, Turner J, Ford MJ et al. Proc Natl Acad Sci USA 1996; 93:6291–6296.
Nishi T, Yoshizato K, Yamashrio S et al. Cancer Res 1996; 56:1050–1055.
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Miller, D.L., Pislaru, S.V. & Greenleaf, J.F. Sonoporation: Mechanical DNA Delivery by Ultrasonic Cavitation. Somat Cell Mol Genet 27, 115–134 (2002). https://doi.org/10.1023/A:1022983907223
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DOI: https://doi.org/10.1023/A:1022983907223